Effect of Monthly, High‐Dose, Long‐Term Vitamin D Supplementation on Central Blood Pressure Parameters: A Randomized Controlled Trial Substudy

Abstract

BackgroundThe effects of monthly, high‐dose, long‐term (≥1‐year) vitamin D supplementation on central blood pressure (BP) parameters are unknown.Methods and ResultsA total of 517 adults (58% male, aged 50–84 years) were recruited into a double‐blinded, placebo‐controlled trial substudy and randomized to receive, for 1.1 years (median; range: 0.9–1.5 years), either (1) vitamin D3 200 000 IU (initial dose) followed 1 month later by monthly 100 000‐IU doses (n=256) or (2) placebo monthly (n=261). At baseline (n=517) and follow‐up (n=380), suprasystolic oscillometry was undertaken, yielding aortic BP waveforms and hemodynamic parameters. Mean deseasonalized 25‐hydroxyvitamin D increased from 66 nmol/L (SD: 24) at baseline to 122 nmol/L (SD: 42) at follow‐up in the vitamin D group, with no change in the placebo group. Despite small, nonsignificant changes in hemodynamic parameters in the total sample (primary outcome), we observed consistently favorable changes among the 150 participants with vitamin D deficiency (<50 nmol/L) at baseline. In this subgroup, mean changes in the vitamin D group (n=71) versus placebo group (n=79) were −5.3 mm Hg (95% confidence interval [CI], −11.8 to 1.3) for brachial systolic BP (P=0.11), −2.8 mm Hg (95% CI, −6.2 to 0.7) for brachial diastolic BP (P=0.12), −7.5 mm Hg (95% CI, −14.4 to −0.6) for aortic systolic BP (P=0.03), −5.7 mm Hg (95% CI, −10.8 to −0.6) for augmentation index (P=0.03), −0.3 m/s (95% CI, −0.6 to −0.1) for pulse wave velocity (P=0.02), −8.6 mm Hg (95% CI, −15.4 to −1.9) for peak reservoir pressure (P=0.01), and −3.6 mm Hg (95% CI, −6.3 to −0.8) for backward pressure amplitude (P=0.01).ConclusionsMonthly, high‐dose, 1‐year vitamin D supplementation lowered central BP parameters among adults with vitamin D deficiency but not in the total sample.Clinical Trial Registration URL: http://www.anzctr.org.au. Unique identifier: ACTRN12611000402943.

Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta‐Analysis

“…Similarly, a recently published substudy using monthly high‐dose vitamin D3 showed an improvement in aortic BP and arterial stiffness measures in those with baseline 25(OH)D levels <50 nmol/L; effect sizes were consistent with our IPD analysis findings for this subgroup. No significant improvements were observed in the overall trial group, however …”

“…No significant improvements were observed in the overall trial group, however. 51 Pooled observational data show that a log e difference in PWV (%2.7 m/s) corresponds to a 35% to 45% increase in the risk of a cardiovascular event. A 0.3-m/s improvement in PWV is therefore unlikely to be associated with a clinically important reduction in cardiovascular events.…”

Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure

“…The Vitamin D Assessment study (ViDA) in 5100 healthy subjects, aged > 50 years, recently reported that 100,000 IU oral vitamin D 3 monthly was neutral for the prevention of CV disease [49,50], with a low rate of 25[OH]D deficiency in participants (25%), a lower than expected endpoint rate and monthly doses cited as possible reasons [51]. Metaanalysis and data from ViDA and other studies describe that benefits on clinical outcomes are greatest in the most deficient, and in studies using daily dosing regimens (as in VINDICATE) rather than monthly [52][53][54][55].…”

Effect of Vitamin D Supplementation on Arterial Stiffness and Central Blood Pressure Indexes: Demystifying the Evidence

“…Data about the effects of vitamin D supplementation on PWV and central BP have been limited . Two studies in this issue of JAHA address this need, by examining the potential benefits of vitamin D supplementation on arterial stiffness and central BP . In BEST‐D (Biochemical Efficacy and Safety Trial of Vitamin D), 305 community‐dwelling older adults living in the United Kingdom were randomized to receive vitamin D 4000 IU, vitamin D 2000 IU, or placebo for 12 months.…”

“…10,11 Two studies in this issue of JAHA address this need, by examining the potential benefits of vitamin D supplementation on arterial stiffness and central BP. 12,13 In BEST-D (Biochemical Efficacy and Safety Trial of Vitamin D), 305 community-dwelling older adults living in the United Kingdom were randomized to receive vitamin D 4000 IU, vitamin D 2000 IU, or placebo for 12 months. The primary end point in BEST-D was plasma 25-hydroxyvitamin D, and the main findings have been published previously.…”